A novel role for autophagy in T cell education.
During T cell development in the thymus, scanning of peptide/major histocompatibility (MHC) molecule complexes on the surface of thymic epithelial cells ensures that only useful (self-MHC restricted) and harmless (self-tolerant) thymocytes survive. In recent years, a number of distinct cell-biological features of thymic epithelial cells have been unraveled that may have evolved to render these cells particularly suited for T cell selection, e.g., cortical epithelial cells use unique proteolytic enzymes for the generation of MHC/peptide complexes, whereas medullary epithelial cells "promiscuously" express otherwise tissue-restricted self-antigens. We recently showed that macroautophagy in thymic epithelial cells contributes to CD4 T cell selection and is essential for the generation of a self-tolerant T cell repertoire. We propose that the unusually high constitutive levels of autophagy in thymic epithelial cells deliver endogenous proteins to MHC class II molecules for both positive and negative selection of developing thymocytes.
Nedjic
Jelena
J
Institute for Immunology, Ludwig-Maximilians-University, Munich, Germany.
Aichinger
Martin
M
Klein
Ludger
L
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D000071187:Autophagy-Related Protein 5; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics; D010455:Peptides / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000949:Histocompatibility Antigens Class II; D008869:Microtubule-Associated Proteins; D010455:Peptides